The effect of antipsychotic medication is poor in 30-40% of patients with schizophrenia; treatment resistance is usually met with shifts to new drugs or drug augmentation strategies or a trial of clozapine. The purpose of this review was to examine the potential role of intestinal bacteria in the bioavailability of antipsychotic medication and the possibility that parenterally administered antipsychotics might be able to overcome treatment resistance. Databases were searched with appropriate terms to locate relevant papers dealing with the effect of antipsychotic drugs on the gut microbiome and the effect of bacterial metabolizing enzymes on antipsychotic drugs. Also searched were papers addressing the various current parenteral formulations of antipsychotic drugs. Sixty-five recent pertinent papers were reviewed and the results are suggestive of the premise that there is a drug refractory form of psychosis for which the composition of gut bacteria is responsible, and that parenteral drug administration could overcome the problem.